Benzyl-PEG12-Ots , CAS No.B1446759

CAS: B1446759 Cat. No.: B1446759 Formula: C₃₈H₆₂O₁₅S Peso molecolare: 790.95

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Panoramica

Benzyl-PEG12-Ots is a PEG-based PROTAC linker can be used in the synthesis of PROTACs.

Specifications

Condizioni di conservazione di stoccaggio

Store at -20°C

Spedito in

Ice chest + Ice pads

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Nomi e identificatori

Peso molecolare

790.95

Application Protocols

No validated bioassay protocols (WB, IHC, IF, FC, etc.) are applicable to this small-molecule linker.

General lab protocol guidance (for synthetic use):

• Ensure glassware and solvents are dry; pre-dry PEG linkers under vacuum if needed.
• Prepare nucleophile solutions freshly; where applicable, add catalytic iodide or crown ether to enhance SN2 rates.
• Monitor reactions by LC-MS or 1H NMR (disappearance of tosylate-adjacent methylene, appearance of new terminal group signals).
• For workup, dilute with water/brine and extract with EtOAc/MTBE. Remove polar aprotic solvents thoroughly under reduced pressure; co-evaporate with toluene or toluene/MeCN to strip DMF/DMSO traces.

These are general practices and not item-specific use tests. For precise conditions, see the Reaction Conditions tab and adapt to your substrates.

Biological Roles

This product is a synthetic PEG linker and does not have inherent biological activity assigned. Any biological relevance arises from its use as a spacer in conjugates.

General considerations for PEG linkers (literature/background):

• PEG spacers can increase aqueous compatibility, reduce protein adsorption, and modulate hydrodynamic size of conjugates.
• Benzyl terminus is typically used as a protecting/anchoring element rather than for biological interaction; it can be removed (e.g., hydrogenolysis) to liberate a terminal hydroxyl for further derivatization.
• Tosylate end is reactive and not suitable for direct biological exposure; it is intended to be transformed into more biocompatible groups (amines, azides, thiols) prior to any bio-facing application.

Research use only: Any use in biological systems should be preceded by conversion to stable, biocompatible functionalities and thorough purification. No clinical or therapeutic claims are made or implied for this item.

Buffer Applications

Not typically applicable. Benzyl-PEG12-Ots is a synthetic organic linker and does not serve as a buffering agent or pH stabilizer.

Practical note: If used in bioconjugation workflows, buffering is relevant only after conversion to a stable functionality (e.g., amine/azide/thiol) and attachment to biomolecules; in those cases, select buffers that do not compete with or quench the reactive partner (e.g., avoid primary amine buffers during NHS-ester couplings).

Green Alternatives

Greener choices relate primarily to solvent selection and leaving-group strategy; the PEG12 framework itself is generally considered benign, but end-groups determine process hazards.

• Solvent alternatives (literature/principles):

  • Replace DMF/NMP with acetonitrile, 2‑MeTHF, or CPME when solubility allows; these can lower reproductive toxicity concerns (vs DMF/NMP) and facilitate workup.
  • Use water/MeCN biphasic systems with phase-transfer catalysts for some halide/azide substitutions to reduce dipolar aprotic solvent usage.
  • Consider propyl/ethyl acetate as extraction solvents to avoid chlorinated waste.

• Leaving group alternatives (trade-offs):

  • Mesylate (OMs): more atom-economical and sometimes higher reactivity; however, stability toward hydrolysis may be reduced compared to OTs in some contexts (literature).
  • Carbonates (e.g., p‑nitrophenyl carbonate) for alcohol-terminating PEGs can enable coupling under milder, less hazardous conditions for urethane formation, but may not substitute directly for SN2 chemistry applicable to OTs.

Comparison snapshot (general):

• OTs in DMF: high conversion, excellent substrate scope; environmental/safety drawbacks due to solvent.
• OTs in MeCN or 2‑MeTHF: potentially greener with acceptable rates for many SN2 displacements.
• OMs vs OTs: OMs greener and more volatile by-products; OTs often more robust to storage/handling.

Note: Selection must balance worker safety, waste minimization, and reaction performance. Validate greener alternatives at small scale before process adoption.

Pharmaceutical Uses

No pharmacopeial status or excipient role is specified for this item. It is provided for research and laboratory use only.

General context (non-clinical, formulation research):

• Discrete-length PEG linkers are commonly evaluated in discovery workflows to modulate solubility, permeability, and spatial separation in conjugates or molecular probes.
• The tosylate form is an intermediate and is generally converted to other functionalities (e.g., amines, azides, thiols) before any formulation-like studies are undertaken.

For any application intersecting regulated development, obtain detailed specifications and impurity profiles from the CoA/Spec Sheet and assess suitability under your quality system.

Physical Properties

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight (exact): Not specified for this item; refer to CoA/Spec Sheet.
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point / boiling point: Not specified for this item; refer to CoA/Spec Sheet.
• Density, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.

General/literature expectations for PEG12 tosylates (informational only):

• Physical state: typically a viscous oil to waxy solid at ambient temperature; phase can depend on microstructure and end-groups (literature).
• Solubility: high in polar aprotic organic solvents (DMF, DMSO, NMP, MeCN, THF, DCM); moderate in lower alcohols; water solubility can be limited by the hydrophobic benzyl and tosylate aryl groups despite the PEG12 spacer (literature).
• Partitioning: amphiphilic; PEG chain imparts hydrophilicity while terminal aromatic groups increase hydrophobic character (literature).
• Hygroscopicity: PEG chains are hygroscopic; handle under dry conditions to prevent hydrolysis of the tosylate end-group (practical note).

Note: For any property limits required for regulated workflows (e.g., water content, residual solvents, metal content), consult the item’s CoA/Spec Sheet. Do not infer specifications from literature trends.

Quality and Grades

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Context for this class of product (general guidance):

• Linker-grade PEG tosylates are commonly offered at high purity to support downstream coupling efficiency. Purity is typically assessed by NMR and LC/MS or HPLC (literature/industry practice).
• Low residual water is important to preserve tosylate integrity; Karl Fischer values may be provided on the CoA. For this specific item, these are not specified here—consult the CoA.
• Stabilizers: Tosylates generally do not require added stabilizers; quality is preserved by dryness, low temperature, and protection from moisture. No stabilizer is specified for this item.
• What to verify on receipt (best practice):
  • Single major peak by HPLC/LC-MS for monodisperse material.
  • Identity by 1H/13C NMR (PEG multiplets, benzyl signals, tosyl aromatic pattern, methyl singlet).
  • Water content and residual solvents within your method requirements.

If regulatory compliance (e.g., GMP) or specific impurity thresholds are required for your application, contact us with your specifications; otherwise, rely on the CoA/Spec Sheet for item-specific quality attributes.

Reaction and Applications

This linker is designed as a versatile electrophile for constructing PEGylated architectures. The terminal tosylate enables SN2 reactions, while the benzyl end can serve as a removable protecting/anchoring group (literature/practice).

Key transformations (general, literature):

• Azidation: NaN3 or TBA–N3 in DMF/MeCN to form Benzyl‑PEG12‑N3; subsequent CuAAC or Staudinger/hydrogenation reveals amine for further coupling (e.g., amide formation, reductive amination).
• Thiolation: Reaction with thiolates (RS–) gives thioether-linked products; thioacetate displacement followed by hydrolysis is a common route to terminal thiols.
• Ether formation: Alkoxides (RO–) afford extended ethers for surface modification or spacer installation.
• Halide exchange: LiBr/KI substitution to the corresponding bromide/iodide increases reactivity for subsequent couplings.
• Carbon–carbon introduction: Cyanide displacement (carefully, with appropriate safety) to give nitrile-terminated PEGs, enabling further elaboration.

Application domains (research use only):

• Bioconjugation linkers: Introduce a defined-length PEG12 spacer between small molecules, surfaces, or biomacromolecules (e.g., via azide/amine/thio handles generated from the tosylate).
• Materials & surface science: Grafting to oxides/polymers through etherification or thiol–gold interfaces after thiolation.
• Modular assembly: As a spacer in molecular probes and ligand architectures where hydrophilic separation and reduced nonspecific binding are desired.

Practical tips:

• Maintain anhydrous conditions; the tosylate hydrolyzes in wet media.
• Use phase-transfer catalysts (e.g., TBAB) when employing inorganic nucleophiles in less polar solvents.
• For clean workups, exploit PEG’s partitioning by brine salting-out or use minimal polar aprotic co-solvent followed by precipitation in cold ether.

Reaction Conditions

Typical conditions for common transformations (general literature guidance; optimize for your substrate):

• Azidation to Benzyl‑PEG12‑N3:

  • Reagents: NaN3 (3–5 equiv) or TBA–N3; solvent: dry DMF or MeCN.
  • Temperature/time: 60–90°C, 6–24 h.
  • Notes: Add 0.1–0.5 equiv 18‑crown‑6 for inorganic azide in MeCN to enhance rate. Monitor by LC-MS. Typical conversions high; isolated yields often good after minimal purification.

• Thiolation (thioether formation):

  • Reagents: R–SNa (from RSH + base) or KSAc (then hydrolyze to thiol).
  • Solvent: dry DMF or MeCN; Temperature: 0–25°C (sensitive nucleophiles) to 50°C (robust systems).
  • Notes: Limit strong base to reduce elimination; add iodide as catalyst if sluggish (Finkelstein activation in situ).

• Halide exchange:

  • Reagents: LiBr (5–10 equiv) or KI; Solvent: acetone or MeCN.
  • Conditions: reflux (acetone) or 60–80°C (MeCN), 4–16 h.
  • Notes: Bromides/iodides obtained are more reactive but less stable than OTs—store cold and use promptly.

• Etherification (Williamson):

  • Reagents: RO–Na/K generated in situ; Solvent: dry DMF/THF.
  • Conditions: 25–60°C, 4–24 h.
  • Notes: Ensure nucleophile solubility; phase-transfer catalysts help with inorganic bases.

• Debenzylation (to expose terminal alcohol):

  • Conditions: H2 (1 atm), Pd/C (5–10 wt%), MeOH/EtOAc/EtOH, rt to 40°C, 2–16 h.
  • Notes: PEG tolerates hydrogenation well; filter through celite. Protect other reducible groups as needed.

All values are general literature ranges; confirm by small-scale trials. For sensitive applications, consult the CoA for any constraints (e.g., residual water) that could impact reactivity.

Safety and Handling

• GHS classification, signal word, pictograms, H-statements: Not specified for this item; refer to the SDS for authoritative safety information.
• Storage conditions (product data): Store at −20°C.
• Shipping (product data): Shipped in ice chest with ice pads.

General safety considerations for PEG tosylates (informational, defer to SDS):

• Hazards: Tosylate esters and aromatic sulfonates can cause skin/eye irritation; dust/aerosol inhalation should be avoided. PEG chains can enhance dermal spreading—use appropriate containment (literature/practice).
• Incompatibilities: Strong nucleophiles/bases will react with the tosylate; avoid contact except in intended reactions. Avoid prolonged exposure to moisture and protic solvents that promote hydrolysis to the corresponding alcohol.
• PPE: Laboratory coat, nitrile gloves, splash goggles as a baseline; use chemical-resistant gloves if extended contact is anticipated. Work in a fume hood to prevent exposure to vapors/aerosols.
• Handling tips: Maintain anhydrous conditions for synthetic use. Bring cold material to room temperature in a desiccator to minimize condensation. Cap tightly under dry inert gas if possible.
• First aid (overview; consult SDS): Rinse affected skin/eyes with water for ≥15 min. If inhaled, move to fresh air. If ingested, rinse mouth; seek medical attention in all cases of exposure.

Waste: Dispose according to institutional and local regulations for organic sulfonate esters and PEG-containing organics.

Solvent Selection

Benzyl-PEG12-Ots behaves as an amphiphilic electrophile: the PEG chain favors polar media, while the benzyl and tosylate aryl groups add hydrophobic character.

• Preferred solvents for substitutions (literature/practice):
  • DMF, DMSO, NMP: excellent for SN2 with azide, thiolates, alkoxides, and halides due to high dielectric constant and substrate solubilization.
  • Acetonitrile: good for halide exchange and clean SN2 at elevated temperatures; lower viscosity aids handling.
  • THF, 2-MeTHF, dioxane: suitable with soluble nucleophiles/bases; may require phase-transfer catalysts if nucleophile is inorganic.
  • Acetone: useful for bromide substitution (e.g., LiBr) with salting-out effects (literature).
• Protic solvents (MeOH, EtOH): may promote hydrolysis to the alcohol; use only when intentional (e.g., methoxylation) or with careful control.
• Aqueous systems: limited use unless aided by cosolvents or phase-transfer catalysis; tosylate group is moisture sensitive.

Selection guidance:

• For fast azidation: DMF or DMSO at 60–90°C provides high conversions.
• For thiolation: dry DMF/MeCN with preformed thiolate; avoid excess base to minimize elimination.
• For alkoxylation (ether formation): use dry, aprotic solvents with the corresponding alkoxide and non-nucleophilic counterions.

Comparison (general):

• DMF vs MeCN: DMF dissolves inorganic salts better; MeCN simplifies workup and can reduce PEG tailing on silica.
• DMSO vs NMP: DMSO offers higher polarity but can complicate extractions; NMP is higher boiling for elevated-temp operations.

Storage and Reconstitution

• Storage (product data): Store at −20°C.
• Shipping (product data): Shipped in an ice chest with ice pads.
• Research use note: For research use only.

Reconstitution and handling (practical guidance):

• Solvents: Readily dissolves in dry DMF, DMSO, MeCN, THF, DCM; choose anhydrous grades to prevent tosylate hydrolysis.
• Concentration: Prepare stock solutions (e.g., 10–100 mM) in dry solvent; aliquot into moisture-tight vials under inert gas if possible.
• Stability: Tosylates are moisture sensitive; minimize headspace and exposure to humid air. Avoid repeated freeze–thaw of solids and solutions—use single-use aliquots.
• Light: Store protected from light to minimize potential discoloration or degradation of aromatic sulfonate moieties (general precaution).
• Shelf life: Not specified for this item; refer to CoA/Spec Sheet.

If crystallization or increased viscosity occurs upon cold storage, allow to warm to room temperature in a desiccator before opening to avoid moisture condensation. Always re-cap promptly and return to −20°C after use.

Structure and Identity

Benzyl-PEG12-Ots is a monodisperse polyethylene glycol (PEG) linker bearing a benzyl ether at one terminus and a para-toluenesulfonate (tosylate, OTs) leaving group at the other.

• SKU: B1446759
• Product name: Benzyl-PEG12-Ots
• CAS: B1446759 (internal reference)
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.

Structural features (general description):

• Contains a flexible PEG spacer of ~12 ethylene glycol units [–(CH2–CH2–O)12–], providing hydrophilicity and conformational flexibility.
• One terminus is a benzyl ether (Ph–CH2–O–), which can serve as a protecting/anchoring group and is removable under hydrogenolysis (literature).
• The opposite terminus is a primary tosylate (–O–SO2–C6H4–CH3), a good leaving group for SN2 substitutions (literature).
• Overall architecture: aromatic–ether–(PEG)12–O–SO2–aryl. No stereocenters; polymer-like, but discrete-length linker.

2D structure in words (general):

• A para-methylphenylsulfonyl group connected via sulfonate to the terminal PEG oxygen; the PEG chain extends as alternating –CH2–CH2–O– units and terminates in an ether bond to a benzyl group (phenyl–CH2–).

Synthetic Utility

Functional elements and reactivity (general/literature):

• Primary tosylate (–OTs): excellent leaving group for SN2, enabling installation of a broad set of nucleophiles (N, O, S, X, C). Typically minimal steric hindrance at the terminal PEG carbon enhances reactivity.
• Benzyl ether terminus: acts as a protecting handle; readily cleaved by catalytic hydrogenolysis (H2, Pd/C) to reveal a terminal alcohol for carbonate/ester/ether formation.
• PEG12 spacer: imparts flexibility and hydrophilicity, reduces aggregation and enhances aqueous compatibility of the final constructs.

Representative transformations:

• Nucleophilic substitutions: NaN3 → azide; NaSR/KSR → thioethers; RO–M+ → ethers; CN– → nitrile; LiBr/KI → halides.
• Divergent synthesis: Convert OTs → azide → amine (via hydrogenation or Staudinger reduction) to access amide coupling chemistry.
• Orthogonal strategies: Preserve benzyl-ether end during SN2 on the tosylate; later unmask the benzyl-protected alcohol independently.

Retrosynthetic value:

• Serves as a modular spacer that connects hydrophobic motifs (via benzyl/aryl interactions) with polar domains, aiding solubility tuning and spatial arrangement in multi-component assemblies.

Workup/purification tips:

• Minimize emulsions by salting-out (brine) and using MeCN/EtOAc for extractions. PEG materials often elute late on silica; gradient with polar modifiers (MeOH/DCM or MeOH/EtOAc) or reverse-phase methods can be effective.

Target Specificity

Not applicable. This product is a small-molecule PEG linker and does not possess biological target specificity (no antigen/epitope, clone, or isotype information).